The mammalian cell is now known to utilize the codons UAA, UAG and UGA for peptide chain termination. This finding predicts the occurrence of premature peptide chain termination (nonsense) mutations in the mammalian cell. This proposal outlines a means of inducing and identifying nonsense mutations in Chinese hamster cells and Sindbis virus grown in culture. Chinese hamster cells will then be identified which carry suppressors for these mutations. A combination of viral and cellular genetic and biochemical and immunologic techniques are to be employed. Furthermore, our studies into the mechanism of peptide chain terminations will be continued, using rabbit reticulocyte extracts. They will focus specifically upon the role of GTP, mechanism of peptidyl-tRNA hydrolysis, and number of recognition molecules involved in mammalian peptide chain termination. This dual approach to understanding mammalian nonsense suppression and peptide chain termination will provide maximal understanding for correcting nonsense mutations in man.